tbuckley/cabot-search huggingface dataset:
Multi-omics data reveals aberrant gut microbiota-host glycerophospholipid metabolism in association with neuroinflammation in APP/PS1 mice
Authors: Xiaohang Qian, Wangxi Hai, Siyue Chen, Miao Zhang, Xufeng Jiang, Huidong Tang
Journal: Gut Microbes (2023)

Numerous studies have described the notable impact of gut microbiota on the brain in Alzheimer's disease (AD) via the gut – brain axis. However, the molecular mechanisms underlying the involvement of gut microbiota in the development of AD are limited. This study aimed to explore the potential mechanisms of gut microbiota in AD by integrating multi-omics data. In this study, APP/PS1 and WT mice at nine months of age were used as study mouse model. Cognitive function was assessed using the Morris water maze test. The levels of Aβ plaque and neuroinflammation in the brain were detected using immunofluorescence and PET/CT. In addition, we not only used 16S rRNA gene sequencing and metabolomics to explore the variation characteristics of gut microbiota and serum metabolism abundance, but also combined spatial metabolomics and transcriptomics to explore the change in the brain and identify their potential correlation. APP/PS1 mice showed significant cognitive impairment and amyloid-β deposits in the brain. The abundance of gut microbiota was significantly changed in APP/PS1 mice, including decreased Desulfoviobrio, Enterococcus, Turicibacter, and Ruminococcus and increased Pseudomonas. The integration of serum untargeted metabolomics and brain spatial metabolomics showed that glycerophospholipid metabolism was a common alteration pathway in APP/PS1 mice. Significant proliferation and activation of astrocyte and microglia were observed in APP/PS1 mice, accompanied by alterations in immune pathways. Integration analysis and fecal microbiota transplantation (FMT) intervention revealed potential association of gut microbiota, host glycerophospholipid metabolism, and neuroinflammation levels in APP/PS1 mice.
Gut-derived ammonia contributes to alcohol-related fatty liver development via facilitating ethanol metabolism and provoking ATF4-dependent de novo lipogenesis activation
Authors: Qing Song, Chueh-Lung Hwang, Yanhui Li, Jun Wang, Jooman Park, Samuel M. Lee, Zhaoli Sun, Jun Sun, Yinglin Xia, Natalia Nieto, Jose Cordoba-Chacon, Yuwei Jiang, Xiaobing Dou, Zhenyuan Song
Journal: Metabolism (2023)
Increasing incidence of community-acquired adult group A streptococcal meningitis in the Netherlands
Authors: Evelien H.G.M. Drost, Nora Chekrouni, Thijs M. van Soest, Kim Schipper, Nina M. van Sorge, Matthijs C. Brouwer, Diederik van de Beek
Journal: Journal of Infection (2023)

Dear editor,
Phl p 5 levels more strongly associated than grass pollen counts with allergic respiratory health
Authors: Elaine Fuertes, Debbie Jarvis, Holly Lam, Bethan Davies, Daniela Fecht, Joana Candeias, Carsten B. Schmidt-Weber, Abdel Douiri, Anna Slovick, Enrico Scala, Thomas E.L. Smith, Mohamed Shamji, Jeroen T.M. Buters, Lorenzo Cecchi, Stephen J. Till
Journal: Journal of Allergy and Clinical Immunology (2023)

Studies have linked daily pollen counts to respiratory allergic health outcomes, but few have considered allergen levels.
A small molecule chaperone rescues keratin-8 mediated trafficking of misfolded podocin to correct genetic Nephrotic Syndrome
Authors: Valeryia Kuzmuk, Iwona Pranke, Ruth Rollason, Matthew Butler, Wen Y. Ding, Matthew Beesley, Aoife M. Waters, Richard J. Coward, Richard Sessions, Jack Tuffin, Rebecca R. Foster, Géraldine Mollet, Corinne Antignac, Aleksander Edelman, Gavin I. Welsh, Moin A. Saleem
Journal: Kidney International (2023)

Podocin is a key membrane scaffolding protein of the kidney podocyte essential for intact glomerular filtration. Mutations in NPHS2, the podocin-encoding gene, represent the commonest form of inherited nephrotic syndrome (NS), with early, intractable kidney failure. The most frequent podocin gene mutation in European children is R138Q, causing retention of the misfolded protein in the endoplasmic reticulum. Here, we provide evidence that podocin R138Q (but not wild-type podocin) complexes with the intermediate filament protein keratin 8 (K8) thereby preventing its correct trafficking to the plasma membrane. We have also identified a small molecule (c407), a compound that corrects the Cystic Fibrosis Transmembrane Conductance Regulator protein defect, that interrupts this complex and rescues mutant protein mistrafficking. This results in both the correct localization of podocin at the plasma membrane and functional rescue in both human patient R138Q mutant podocyte cell lines, and in a mouse inducible knock-in model of the R138Q mutation. Importantly, complete rescue of proteinuria and histological changes was seen when c407 was administered both via osmotic minipumps or delivered orally prior to induction of disease or crucially via osmotic minipump two weeks after disease induction. Thus, our data constitute a therapeutic option for patients with NS bearing a podocin mutation, with implications for other misfolding protein disorders. Further studies are necessary to confirm our findings.
Prolonged Gastrointestinal Manifestations After Recovery From COVID-19
Authors: B. Joseph Elmunzer, Olafur S. Palsson, Nauzer Forbes, Ali Zakaria, Christian Davis, Andrew Canakis, Emad Qayed, Benjamin Bick, Swati Pawa, William M. Tierney, Caroline G. McLeod, Jason Taylor, Harsh Patel, Robin B. Mendelsohn, Gokul Bala, Ian Sloan, Ambreen A. Merchant, Zachary L. Smith, Morgan A. Sendzischew Shane, Olga C. Aroniadis, Collins O. Ordiah, Johannah M. Ruddy, Magnus Simren, Jan Tack, Douglas Drossman
Journal: Clinical Gastroenterology and Hepatology (2023)
Characterising sources of PM2·5 exposure for school children with asthma: a personal exposure study across six cities in sub-Saharan Africa
Authors: Shanon Lim, Bibie Said, Lindsay Zurba, Gioia Mosler, Emmanuel Addo-Yobo, Olayinka Olufunke Adeyeye, Bernard Arhin, Dimitris Evangelopoulos, Victoria Temitope Fapohunda, Farida Fortune, Chris J Griffiths, Sbekezelo Hlophe, Marian Kasekete, Scott Lowther, Refiloe Masekela, Elizabeth Mkutumula, Blandina Theophil Mmbaga, Hilda Angela Mujuru, Rebecca Nantanda, Lovemore Mzati Nkhalamba, James S Ngocho, Oluwafemi Tunde Ojo, Sandra Kwarteng Owusu, Sunshine Shaibu, Ismail Ticklay, Jonathan Grigg, Benjamin Barratt
Journal: The Lancet Child & Adolescent Health (2023)

Air pollution is the second largest risk to health in Africa, and children with asthma are particularly susceptible to its effects. Yet, there is a scarcity of air pollution exposure data from cities in sub-Saharan Africa. We aimed to identify potential exposure reduction strategies for school children with asthma living in urban areas in sub-Saharan Africa.
Systematic review of early warning signs of relapse and behavioural antecedents of symptom worsening in people living with schizophrenia spectrum disorders
Authors: J.F. Gleeson, T.B. McGuckian, D.K. Fernandez, M.I. Fraser, A. Pepe, R. Taskis, M. Alvarez-Jimenez, J.F. Farhall, A. Gumley
Journal: Clinical Psychology Review (2023)

Identification of the early warning signs (EWS) of relapse is key to relapse prevention in schizophrenia spectrum disorders, however, limitations to their precision have been reported. Substantial methodological innovations have recently been applied to the prediction of psychotic relapse and to individual psychotic symptoms. However, there has been no systematic review that has integrated findings across these two related outcomes and no systematic review of EWS of relapse for a decade.
Impact of the COVID-19 pandemic on antibiotic prescribing in high-prescribing primary care physicians in Switzerland
Authors: Soheila Aghlmandi, Florian S. Halbeisen, Pascal Godet, Andri Signorell, Simon Sigrist, Ramon Saccilotto, Andreas F. Widmer, Andreas Zeller, Julia Bielicki, Heiner C. Bucher
Journal: Clinical Microbiology and Infection (2023)
Therapeutic targeting of EP300/CBP by bromodomain inhibition in hematologic malignancies
Authors: Luciano Nicosia, Gary J. Spencer, Nigel Brooks, Fabio M.R. Amaral, Naseer J. Basma, John A. Chadwick, Bradley Revell, Bettina Wingelhofer, Alba Maiques-Diaz, Oliver Sinclair, Francesco Camera, Filippo Ciceri, Daniel H. Wiseman, Neil Pegg, Will West, Tomasz Knurowski, Kris Frese, Karen Clegg, Victoria L. Campbell, James Cavet, Mhairi Copland, Emma Searle, Tim C.P. Somervaille
Journal: Cancer Cell (2023)

CCS1477 (inobrodib) is a potent, selective EP300/CBP bromodomain inhibitor which induces cell-cycle arrest and differentiation in hematologic malignancy model systems. In myeloid leukemia cells, it promotes rapid eviction of EP300/CBP from an enhancer subset marked by strong MYB occupancy and high H3K27 acetylation, with downregulation of the subordinate oncogenic network and redistribution to sites close to differentiation genes. In myeloma cells, CCS1477 induces eviction of EP300/CBP from FGFR3, the target of the common (4; 14) translocation, with redistribution away from IRF4-occupied sites to TCF3/E2A-occupied sites. In a subset of patients with relapsed or refractory disease, CCS1477 monotherapy induces differentiation responses in AML and objective responses in heavily pre-treated multiple myeloma. In vivo preclinical combination studies reveal synergistic responses to treatment with standard-of-care agents. Thus, CCS1477 exhibits encouraging preclinical and early-phase clinical activity by disrupting recruitment of EP300/CBP to enhancer networks occupied by critical transcription factors.
Temporal evolution reveals bifurcated lineages in aggressive neuroendocrine small cell prostate cancer trans-differentiation
Authors: Chia-Chun Chen, Wendy Tran, Kai Song, Tyler Sugimoto, Matthew B. Obusan, Liang Wang, Katherine M. Sheu, Donghui Cheng, Lisa Ta, Grigor Varuzhanyan, Arthur Huang, Runzhe Xu, Yuanhong Zeng, Amirreza Borujerdpur, Nicholas A. Bayley, Miyako Noguchi, Zhiyuan Mao, Colm Morrissey, Eva Corey, Peter S. Nelson, Yue Zhao, Jiaoti Huang, Jung Wook Park, Owen N. Witte, Thomas G. Graeber
Journal: Cancer Cell (2023)

Trans-differentiation from an adenocarcinoma to a small cell neuroendocrine state is associated with therapy resistance in multiple cancer types. To gain insight into the underlying molecular events of the trans-differentiation, we perform a multi-omics time course analysis of a pan-small cell neuroendocrine cancer model (termed PARCB), a forward genetic transformation using human prostate basal cells and identify a shared developmental, arc-like, and entropy-high trajectory among all transformation model replicates. Further mapping with single cell resolution reveals two distinct lineages defined by mutually exclusive expression of ASCL1 or ASCL2. Temporal regulation by groups of transcription factors across developmental stages reveals that cellular reprogramming precedes the induction of neuronal programs. TFAP4 and ASCL1/2 feedback are identified as potential regulators of ASCL1 and ASCL2 expression. Our study provides temporal transcriptional patterns and uncovers pan-tissue parallels between prostate and lung cancers, as well as connections to normal neuroendocrine cell states.
Cardiac PET Myocardial Blood Flow Quantification Assessment of Early Cardiac Allograft Vasculopathy
Authors: Sharon Chih, Anahita Tavoosi, Vidhya Nair, Aun Yeong Chong, Vladimír Džavík, Natasha Aleksova, Derek Y. So, Robert A. deKemp, Ines Amara, George A. Wells, Jordan Bernick, Christopher B. Overgaard, Emel Celiker-Guler, Lisa M. Mielniczuk, Ellamae Stadnick, Caroline McGuinty, Heather J. Ross, Rob S.B. Beanlands
Journal: JACC. Cardiovascular imaging (2023)
Prevention of incisional hernia with prophylactic onlay and sublay mesh reinforcement vs. primary suture only in midline laparotomies (PRIMA): long-term outcomes of a multicentre, double-blind, randomised controlled trial
Authors: Louis Matthijs Van den Dop, Dimitri Sneiders, Yagmur Yurtkap, Alexander Werba, David van Klaveren, Robert E.G.J.M. Pierik, Daniel Reim, Lucas Timmermans, René H. Fortelny, André L. Mihaljevic, Gert-Jan Kleinrensink, Pieter J. Tanis, Johan F. Lange, Johannes Jeekel, Rainier Grotelüschen, Rudie Roumen, Laurens van Baardewijk, Jerome van Brussel, Michiel van den Berg, Martijn Boomsma, Roy Dwarkasing, Maarten van der Wal, Steven Buijk, An Jairam, Pim C.W. Burger, Hence Verhagen, D. De Jong, Pieter Klitsie, Lenny Lases, Arie van der Ham, Joris Harlaar, Jan Charbon, Bart Leenders, Imro Dawson, Christof Seiler, Markus Buchler, Markus Diener, Christoph Schuhmacher, Jakob Izbicki, Asad Kutup, Peter Neuhaus, Panagiotis Fikatas, Markus Golling, Dirk Laux, Christopher May, Jeroen Nieuwenhuizen, Hasan H. Eker
Journal: The Lancet Regional Health - Europe (2023)

Incisional hernia occurs approximately in 40% of high-risk patients after midline laparotomy. Prophylactic mesh placement has shown promising results, but long-term outcomes are needed. The present study aimed to assess the long-term incisional hernia rates of the previously conducted PRIMA trial with radiological follow-up. In the PRIMA trial, patients with increased risk of incisional hernia formation (AAA or BMI ≥27 kg/m2) were randomised in a 1:2:2 ratio to primary suture, onlay mesh or sublay mesh closure in three different countries in eleven institutions. Incisional hernia during follow-up was diagnosed by any of: CT, ultrasound and physical examination, or during surgery. Assessors and patients were blinded until 2-year follow-up. Time-to-event analysis according to intention-to-treat principle was performed with the Kaplan–Meier method and Cox proportional hazard models. Trial registration: NCT00761475 (ClinicalTrials.gov). Between 2009 and 2012, 480 patients were randomized: 107 primary suture, 188 onlay mesh and 185 sublay mesh. Five-year incisional hernia rates were 53.4% (95% CI: 40.4–64.8), 24.7% (95% CI: 12.7–38.8), 29.8% (95% CI: 17.9–42.6), respectively. Compared to primary suture, onlay mesh (HR: 0.390, 95% CI: 0.248–0.614, p < 0.001) and sublay mesh (HR: 0.485, 95% CI: 0.309–0.761, p = 0.002) were associated with a significantly lower risk of incisional hernia development. Prophylactic mesh placement remained effective in reducing incisional hernia occurrence after midline laparotomy in high-risk patients during long-term follow-up. Hernia rates in the primary suture group were higher than previously anticipated. B. Braun.
Evaluation of the effectiveness of a nationwide precision medicine program for patients with advanced non-small cell lung cancer in Germany: a historical cohort analysis
Authors: Anika Kästner, Anna Kron, Neeltje van den Berg, Kilson Moon, Matthias Scheffler, Gerhard Schillinger, Natalie Pelusi, Nils Hartmann, Damian Tobias Rieke, Susann Stephan-Falkenau, Martin Schuler, Martin Wermke, Wilko Weichert, Frederick Klauschen, Florian Haller, Horst-Dieter Hummel, Martin Sebastian, Stefan Gattenlöhner, Carsten Bokemeyer, Irene Esposito, Florian Jakobs, Christof von Kalle, Reinhard Büttner, Jürgen Wolf, Wolfgang Hoffmann
Journal: The Lancet Regional Health - Europe (2023)

The national Network Genomic Medicine (nNGM) Lung Cancer provides comprehensive and high-quality multiplex molecular diagnostics and standardized personalized treatment recommendation for patients with advanced non-small cell lung cancer (aNSCLC) in Germany. The primary aim of this study was to investigate the effectiveness of the nNGM precision medicine program in terms of overall survival (OS) using real-world data (RWD).A historical nationwide cohort analysis of patients with aNSCLC and initial diagnosis between 04/2019 and 06/2020 was conducted to compare treatment and OS of patients with and without nNGM-participation. Patients participating within the nNGM (nNGM group) were selected based on a prospective nNGM database. The electronic health records (EHR) of the prospective nNGM database were case-specifically linked to claims data (AOK, German health insurance). The control group was selected from claims data of patients receiving usual care without nNGM-participation (non-nNGM group). The minimum follow-up period was six months.Overall, n = 509 patients in the nNGM group and n = 7213 patients in the non-nNGM group met the inclusion criteria. Patients participating in the nNGM had a significantly improved OS compared to the non-nNGM group (median OS: 10.5 months vs. 8.7 months, p = 0.008, HR = 0.84, 95% CI: 0.74-0.95). The 1-year survival rates were 46.8% (nNGM) and 41.3% (non-nNGM). The use of approved tyrosine kinase inhibitors (TKI) in the first-line setting was significantly higher in the nNGM group than in the non-nNGM group (nNGM: 8.4% (43/509) vs. non-nNGM: 5.1% (366/7213), p = 0.001). Overall, patients receiving first-line TKI treatment had significantly higher 1-year OS rates than patients treated with PD-1/PD-L1 inhibitors and/or chemotherapy (67.2% vs. 40.2%, p < 0.001).This is the first study to demonstrate a significant survival benefit and higher utilization of targeted therapies for aNSCLC patients participating within nNGM. Our data indicate that precision medicine programs can enhance collaborative personalized lung cancer care and promote the implementation of treatment innovations and the latest scientific knowledge into clinical routine care.The study was funded by the AOK Federal Association Germany.
Impact of mandatory preoperative dental screening on post-procedural risk of infective endocarditis in patients undergoing transcatheter aortic valve implantation: a nationwide retrospective observational study
Authors: Lytfi Krasniqi, Lars Peter Schødt Riber, Henrik Nissen, Christian Juhl Terkelsen, Niels Holmark Andersen, Phillip Freeman, Jonas A. Povlsen, Oke Gerke, Marie-Annick Clavel, Jordi Sanchez Dahl
Journal: The Lancet Regional Health - Europe (2023)

Guidelines recommend preoperative dental screening (PDS) prior to cardiac valve surgery, to reduce the incidence of prosthetic valve infective endocarditis (IE). However, limited data support these recommendations, particular in patients undergoing transcatheter aortic valve implantation (TAVI). We aimed to investigate the effect of mandatory PDS on risk of IE in patients undergoing TAVI. In this observational study, a total of 1133 patients undergoing TAVI in Western-Denmark from 2020 to 2022 were included. Patients were categorized based on two implemented PDS practices: mandatory PDS (MPDS group), and no referral for PDS (NPDS group). Outcome data were retrieved from Danish registries and confirmed using medical records. The primary outcome was incidence of IE. Secondary outcomes were all-cause mortality and composite outcome of all-cause mortality and IE. Of 568 patients in the MPDS group 126 (22.2%) underwent subsequent oral dental surgery, compared to 8 (1.4%) among 565 patients in the NPDS group. During a median follow-up of 1.9 years (interquartile range 1.4–2.5 years), 31 (2.7%) developed IE. The yearly incidence IE rate was 1.4% (0.8–2.3) and 1.5% (0.8–2.4) in MPDS and NPDS, respectively, p = 0.86. All-cause mortality rates were similar between groups (estimated 2-year overall mortality of 6.7% (4.8–9.2) vs. 4.7% (3.2–6.9), MPDS and NPDS, respectively, p = 0.15). Consistent findings were found in 712 propensity score-matched patients. Mandatory PDS did not demonstrate reduced risk of IE or all-cause mortality compared to targeted PDS in patients undergoing TAVI. The funder had no role in the study design, data management, or writing.
Rationale and design of the <scp>ESC</scp> Heart Failure <scp>III</scp> Registry – Implementation and discovery
Authors: Lars H. Lund, Maria Generosa Crespo‐Leiro, Cecile Laroche, Jose M. Garcia‐Pinilla, Ahmed Bennis, Eleonora B. Vataman, Marija Polovina, Slavica Radovanovic, Svetlana R. Apostolovic, Milika Ašanin, Andrzej Gackowski, Agnieszka Kaplon‐Cieslicka, Irina Cabac‐Pogorevici, Stefan D. Anker, Ovidiu Chioncel, Andrew J.S. Coats, Gerasimos Filippatos, Mitja Lainscak, Theresa Mcdonagh, Alexandre Mebazaa, Marco Metra, Massimo Piepoli, Giuseppe M. Rosano, Frank Ruschitzka, Gianluigi Savarese, Petar M. Seferović, Bernard Iung, Bogdan A. Popescu, Aldo P. Maggioni
Journal: European Journal of Heart Failure (2023)

Heart failure outcomes remain poor despite advances in therapy. The European Society of Cardiology Heart Failure III Registry (ESC HF III Registry) aims to characterize HF clinical features and outcomes and to assess implementation of guideline-recommended therapy in Europe and other ESC affiliated countries.
Obesity in heart failure with preserved ejection fraction: Insights from the <scp>REDUCE LAP‐HF II</scp> trial
Authors: Sheldon E. Litwin, Jan Komtebedde, Tim Seidler, Barry A. Borlaug, Sebastian Winkler, Scott D. Solomon, Jean‐Christophe Eicher, Sula Mazimba, Rami Khawash, Aaron L. Sverdlov, Scott L. Hummel, Heiko Bugger, Florian Boenner, Elke Hoendermis, Maja Cikes, Catherine Demers, Guillherme Silva, Vanessa van Empel, Randall C. Starling, Martin Penicka, Donald E. Cutlip, Martin B. Leon, Dalane W. Kitzman, Dirk J. van Veldhuisen, Sanjiv J. Shah
Journal: European Journal of Heart Failure (2023)
P0.1 During Pressure Support Ventilation
Authors: Joanna W. Y. Chow, Wisam Al-Bassam, Fumitaka Yanase, Zachary O’Brien, Ahmad Bassam, Stefanos Hadzakis, Anis Chaba, Akinori Maeda, Rinaldo Bellomo, Ary Serpa Neto, Joanna W. Y. Chow, Wissam Al-Basam, Fumitaka Yanase, Zachary O’Brien, Ahmad Bassam, Anis Chaba, Sofia Spano, Akinori Maeda, Lucinda Roberts, Glenn Eastwood, Stefanos Hadzakis, Rinaldo Bellomo, Ary Serpa Neto
Journal: American Journal of Respiratory and Critical Care Medicine (2023)
COVID‐19 cooling: Nanostrategies targeting cytokine storm for controlling severe and critical symptoms
Authors: Yu Zheng, Yuke Li, Mao Li, Rujing Wang, Yuhong Jiang, Mengnan Zhao, Jun Lu, Rui Li, Xiaofang Li, Sanjun Shi
Journal: Medicinal Research Reviews (2023)

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to wreak havoc worldwide, the "Cytokine Storm" (CS, also known as the inflammatory storm) or Cytokine Release Syndrome has reemerged in the public consciousness. CS is a significant contributor to the deterioration of infected individuals. Therefore, CS control is of great significance for the treatment of critically ill patients and the reduction of mortality rates. With the occurrence of variants, concerns regarding the efficacy of vaccines and antiviral drugs with a broad spectrum have grown. We should make an effort to modernize treatment strategies to address the challenges posed by mutations. Thus, in addition to the requirement for additional clinical data to monitor the long-term effects of vaccines and broad-spectrum antiviral drugs, we can use CS as an entry point and therapeutic target to alleviate the severity of the disease in patients. To effectively combat the mutation, new technologies for neutralizing or controlling CS must be developed. In recent years, nanotechnology has been widely applied in the biomedical field, opening up a plethora of opportunities for CS. Here, we put forward the view of cytokine storm as a therapeutic target can be used to treat critically ill patients by expounding the relationship between coronavirus disease 2019 (COVID-19) and CS and the mechanisms associated with CS. We pay special attention to the representative strategies of nanomaterials in current neutral and CS research, as well as their potential chemical design and principles. We hope that the nanostrategies described in this review provide attractive treatment options for severe and critical COVID-19 caused by CS.